Genetics, Vol. 153, 361-382, September 1999, Copyright © 1999

The Catecholamines up (Catsup) Protein of Drosophila melanogaster Functions as a Negative Regulator of Tyrosine Hydroxylase Activity

Dean G. Stathakisa, Denise Y. Burtonb, Wilson E. McIvora, Sujatha Krishnakumarb, Theodore R. F. Wrighta, and Janis M. O'Donnellb
a Department of Biology, University of Virginia, Charlottesville, Virginia 22903-2477
b Department of Biological Sciences and Coalition for Biomolecular Products, University of Alabama, Tuscaloosa, Alabama 35487-0344

Corresponding author: Dean G. Stathakis, University of California, Department of Developmental and Cell Biology, 4150 Biological Sciences II, Irvine, CA 92697-2275., dgstatha{at}uci.edu (E-mail)

Communicating editor: V. G. FINNERTY

We report the genetic, phenotypic, and biochemical analyses of Catecholamines up (Catsup), a gene that encodes a negative regulator of tyrosine hydroxylase (TH) activity. Mutations within this locus are semidominant lethals of variable penetrance that result in three broad, overlapping effective lethal phases (ELPs), indicating that the Catsup gene product is essential throughout development. Mutants from each ELP exhibit either cuticle defects or catecholamine-related abnormalities, such as melanotic salivary glands or pseudotumors. Additionally, Catsup mutants have significantly elevated TH activity that may arise from a post-translational modification of the enzyme. The hyperactivation of TH in Catsup mutants results in abnormally high levels of catecholamines, which can account for the lethality, visible phenotypes, and female sterility observed in these mutants. We propose that Catsup is a component of a novel system that downregulates TH activity, making Catsup the fourth locus found within the Dopa decarboxylase (Ddc) gene cluster that functions in catecholamine metabolism.





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